Members of the S100 protein family are low molecular mass acidic proteins characterized by cell-type-specific expression and the presence of 2 EF-hand calcium-binding domains. The calgranulins are S100 proteins that are expressed in neutrophils, and are abundant in infiltrating monocytes and granulocytes under conditions of chronic inflammation.
Hofmann et al. (1999) reported that RAGE is a central cell surface receptor for S100A12, which they referred to as EN-RAGE (Extracellular Newly identified RAGE-binding protein), and related members of the S100/calgranulin superfamily. Interaction of EN-RAGE (S100A12) with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggered cellular activation, with generation of key proinflammatory mediators. In murine models, blockade of ENRAGE/RAGE quenched delayed-type hypersensitivity and inflammatory colitis by arresting activation of central signaling pathways and expression of inflammatory gene mediators.
S100A12 serum concentrations indicate neutrophil activation in JRA, cystic fibrosis, Kawasaki disease and Crohn's disease. Its function as a proinflammatory factor secreted by activated neutrophils makes this protein a potential target for future therapies.